title: Mutated beta-catenin evades a microRNA-dependent regulatory loop.
abstract: hsa-mir-483 is located within intron 2 of the IGF2 gene. We have previously shown oncogenic features of miR-483-3p through cooperation with IGF2 or by independently targeting the proapoptotic gene BBC3/PUMA. Here we demonstrate that expression of miR-483 can be induced independently of IGF2 by the oncoprotein β-catenin through an interaction with the basic helix-loop-helix protein upstream stimulatory transcription factor 1. We also show that β-catenin itself is a target of miR-483-3p, triggering a negative regulatory loop that becomes ineffective in cells harboring an activating mutation of β-catenin. These results provide insights into the complex regulation of the IGF2/miR-483 locus, revealing players in the β-catenin pathway.
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Angelo
authors.initials: A
authors.lastname: Veronese
authors.forename: Rosa
authors.initials: R
authors.lastname: Visone
authors.forename: Jessica
authors.initials: J
authors.lastname: Consiglio
authors.forename: Mario
authors.initials: M
authors.lastname: Acunzo
authors.forename: Laura
authors.initials: L
authors.lastname: Lupini
authors.forename: Taewan
authors.initials: T
authors.lastname: Kim
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferracin
authors.forename: Francesca
authors.initials: F
authors.lastname: Lovat
authors.forename: Elena
authors.initials: E
authors.lastname: Miotto
authors.forename: Veronica
authors.initials: V
authors.lastname: Balatti
authors.forename: Lucilla
authors.initials: L
authors.lastname: D'Abundo
authors.forename: Laura
authors.initials: L
authors.lastname: Gramantieri
authors.forename: Luigi
authors.initials: L
authors.lastname: Bolondi
authors.forename: Yuri
authors.initials: Y
authors.lastname: Pekarsky
authors.forename: Danilo
authors.initials: D
authors.lastname: Perrotti
authors.forename: Massimo
authors.initials: M
authors.lastname: Negrini
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D056426:Genetic Loci / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D007438:Introns / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; C035170:IGF2 protein, human; C548912:MIRN483 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D051176:beta Catenin; D007335:Insulin-Like Growth Factor II